The development of effective drug delivery systems is a key focus in pharmaceutical research, aiming to enhance therapeutic efficacy while minimizing adverse effects. Self-assembled nanostructures present a promising solution due to their tunable properties, biocompatibility, and ability to encapsulate and deliver therapeutic agents to specific targets. This review examines recent advancements in drug-based self-assembled nanostructures for targeted delivery applications, including drug-drug conjugates, polymeric-based architectures, biomolecules, peptides, DNA, squalene conjugates and amphiphilic drugs. Various strategies for fabricating these nanostructures are discussed, with an emphasis on the design principles and mechanisms underlying their self-assembly and potential for targeted drug delivery to specific tissues or cells. Furthermore, the integration of targeting ligands, stimuli-responsive moieties and imaging agents into these nanostructures is explored for enhanced therapeutic outcomes and real-time monitoring. Challenges such as stability, scalability and regulatory hurdles in translating these nanostructures from bench to bedside are also addressed. Drug-based self-assembled nanostructures represent a promising platform for developing next-generation targeted drug delivery systems with improved therapeutic efficacy and reduced side effects.